Prostate Cancer is the second most common cause of cancer deaths in men in the United States. It is estimated that 220,900 American men will be diagnosed with prostate cancer this year alone. At the present time, treatment options prolong life; however, all patients will eventually die from advanced disease. Androgen ablation therapy slows the dissemination of the disease; however, once the cancer changes its androgen status, tumors become refractory to hormonal treatment. The purpose of this project is to develop gene therapy for the treatment of androgen-independent prostate cancer using a prostate-specific replication-competent adenovirus as a vector to deliver apoptosis inducing molecules to localized or distant tumors. Preliminary studies have lead to the development of a promoter (PSES) with high specificity and strong activity in prostate cancer cells. This study will employ the prostate-specific promoter to direct the replication of a chimeric adenovirus to prostate cancer cells. This recombinant virus wilt deliver soluble TRAIL, an inducer of apoptosis, to kill the cancer cells, and the safety and efficacy of this therapy will be evaluated for potential clinical use. This therapy has the potential for combination with current treatment methods to eradicate androgen-independent prostate cancer. [unreadable] [unreadable]